Skip to main content
SpringerLink
Log in

The effects of cimetidine, ranitidine and famotidine on rat hepatic microsomal cytochrome P-450 activities

  • Histamine and the Gastrointestinal Tract
  • Published:
Agents and Actions Aims and scope Submit manuscript

Abstract

It has been questioned whether the interaction of H2-antagonists with cytochrome P-450 that is observedin vitro is also relevant for thein vivo situation. Until now the possibility that cytochrome P-450 may function with different modes of action has been neglected in this respect. We studied the effect of cimetidine, ranitidine and famotidine on the monoxygenase, the oxidase and the peroxidase action of cytochrome P-450. Biotransformation catalyzed by the monoxygenase and oxidase action of cytochrome P-450 was affected by cimetidine (probably via its ligand interaction with cytochrome P-450), whereas metabolism by the peroxidase mode of action of cytochrome P-450 was hardly influenced. Ranitidine and famotidine (both pharmacodynamically more potent than cimetidine) only slightly affected cytochrome P-450 activities.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. U. Klotz and I. W. Reimann,Drug interactions through binding to cytochrome P-450: The experience with H 2-receptor blocking agents. Pharmaceut. Res.2, 59–62 (1983).

    Google Scholar 

  2. A. Bast, E. M. Savenije-Chapel and B. H. Kroes,Inhibition of mono-oxygenase and oxidase activity of rat hepatic cytochrome P-450 by H 2-receptor blockers. Xenobiotica14, 399–408 (1984).

    PubMed  Google Scholar 

  3. J. C. Jensen and R. Gugler,Cimetidine interaction with liver microsomes in vitro and in vivo. Involvement of an activated complex with cytochrome P-450. Biochem. Pharmacol.34, 2141–2146 (1985).

    PubMed  Google Scholar 

  4. B. Ioannoni, S. R. Mason, P. E. B. Reilly and D. J. Winzor,Evidence for induction of hepatic microsomal cytochrome P-450 by cimetidine: Binding and kinetic studies. Arch. Biochem. Biophys.247, 372–383 (1986).

    PubMed  Google Scholar 

  5. A. Bast and G. R. M. M. Haenen,Cytochrome P-450 and glutathione: what is the significance of their interrelationship in lipid peroxidation? Trends biochem. Sci.9, 510–513 (1984).

    Google Scholar 

  6. M. M. Bradford,A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein dye-binding. Anal. Biochem.72, 248–254 (1976).

    PubMed  Google Scholar 

  7. A. Bast and J. Noordhoek,Evaluation and comparison of colorimetric, radiometric and high performance liquid chromatographic assays for aminopyrine-N-demethylation by rat liver microsomes. J. Pharm. Pharmacol.33, 14–18 (1981).

    PubMed  Google Scholar 

  8. E. Rekka, G. J. Sterk, H. Timmerman and A. Bast,Identification of structural characteristics of some potential H 2-receptor antagonists that determine the interaction with hepatic cytochrome P-450. Chem.-Biol. Interact.67, 117–127 (1988).

    PubMed  Google Scholar 

  9. A. Bast,Is formation of reactive oxygen by cytochrome P-450 perilous and predictable? Trends. pharmacol. Sci.7, 266–270 (1986).

    Google Scholar 

  10. R. W. Estabrook, C. Martin-Wixtrom, Y. Saeki, R. Renneberg, A. Hildebrandt and J. Werringloer,The peroxidatic function of liver microsomal cytochrome P-450: comparison of hydrogen peroxide and NADPH-catalyzed N-demethylation reactions. Xenobiotica14, 87–104 (1984).

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacochemistry, Faculty of Chemistry, Vrije Universiteit, De Boelelaan 1083, 1081, Amsterdam, The Netherlands

    A. Bast, K. Smid & H. Timmerman

Authors
  1. A. Bast
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K. Smid
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. Timmerman
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bast, A., Smid, K. & Timmerman, H. The effects of cimetidine, ranitidine and famotidine on rat hepatic microsomal cytochrome P-450 activities. Agents and Actions 27, 188–191 (1989). https://doi.org/10.1007/BF02222235

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02222235

Keywords

Search

Navigation